title: Abnormal colonic interstitial cells of Cajal in children with anorectal malformations.
abstract: OBJECTIVE
  Constipation is a frequent functional problem in children after operation for all types of anorectal malformations. Although this has been assumed to be caused by hypomotility of the rectosigmoid colon, recent studies have demonstrated generalized colonic hypomotility in children with high or intermediate anomalies. The cause of this disorder is unknown. The aim of this study was to determine whether the observed colonic hypomotility seen in patients with anorectal malformations was caused by defects in distribution or density of interstitial cells of Cajal (ICC), recently identified as 'intestinal pacemaker cells'.
  
  
  METHODS
  Colostomy specimens from 12 patients with high anorectal anomalies (ARM group; age 0 to 14 months) were compared with colostomy specimens from five control patients with nonmotility-related gastrointestinal pathology (age, 1 to 4 months). Specimens were immunohistochemically labelled with antibodies to PGP9.5, a marker for neural tissue, and antibodies to c-kit, a recently characterized marker for interstitial cells of Cajal (ICC).
  
  
  RESULTS
  Ganglion cells were present in all histological specimens. Abnormalities in distribution and density of c-kit-positive ICC were present in 7 of 12 ARM patients. In two ARM patients, ICC were completely absent, and in five patients, ICC density was markedly reduced in circular muscle and at the submucosal border of circular muscle. Only five ARM patients had a distribution of ICC similar to that of control patients.
  
  
  CONCLUSIONS
  Defects in the population of intestinal pacemaker cells may underlie the colonic hypomotility seen in high anorectal malformations and hence may contribute to refractory constipation.
authors.affiliation: Department of Paediatric Surgery, Alder Hey Children's Hospital, Liverpool, England.
authors.forename: S E
authors.initials: SE
authors.lastname: Kenny
authors.forename: M G
authors.initials: MG
authors.lastname: Connell
authors.forename: R J
authors.initials: RJ
authors.lastname: Rintala
authors.forename: C
authors.initials: C
authors.lastname: Vaillant
authors.forename: D H
authors.initials: DH
authors.lastname: Edgar
authors.forename: D A
authors.initials: DA
authors.lastname: Lloyd
mesh_terms: D001006:Anus, Imperforate / Q000473:pathology* / Q000601:surgery; D016022:Case-Control Studies; D012809:Colon, Sigmoid / Q000473:pathology*; D003125:Colostomy; D003248:Constipation / Q000209:etiology; D005769:Gastrointestinal Motility; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D009419:Nerve Tissue Proteins / Q000032:analysis; D011183:Postoperative Complications / Q000209:etiology; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D013869:Thiolester Hydrolases / Q000032:analysis; D043222:Ubiquitin Thiolesterase
chemical_list: D009419:Nerve Tissue Proteins; D019009:Proto-Oncogene Proteins c-kit; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase